PROJECT SUMMARY/ ABSTRACT Otitis Media is one of the most common diseases seen in pediatric practice and the most frequent reason children consume antibiotics or undergo surgery. Acute otitis media (AOM) is a polymicrobial disease and its pathogenesis involves complex interactions between bacteria, viruses, and the host inflammatory response. The disease mostly occurs as a complication of viral upper respiratory tract infection (URI). AOM bacterial pathogens colonize the respiratory tract but do no harm until viral URI occurs; the URI-associated inflammation leads to dysfunction of the Eustachian tube, which facilitates entry of the colonized bacterial pathogens and/or URI virus into the middle ear. The upper respiratory tract is sterile at birth, but infants gradually acquire complex bacterial communities during the first months of life. Several hundred different types of bacteria, both pathogens and commensals, can potentially colonize the upper respiratory tract. Early colonization with AOM bacterial pathogens is highly associated with early AOM onset and recurrent and chronic otitis later in life. Data have shown interactions among colonizing bacterial pathogens and competition between pathogen- and commensal- colonization in the nasopharynx. One way to prevent bacterial AOM is to reduce pathogen colonization by enhancing commensal colonization. To reach this goal, a better understanding of the complex interactions of the nasopharyngeal microbiota is needed. Dr. Chonmaitree is a pediatric infectious disease physician who has performed extensive research on AOM pathogenesis. Her long-term research goals are to elucidate the contribution of infectious pathogens, and their complex interactions with other otitis risk factors in the pathogenesis of and recovery from AOM, and to identify possible strategies for more effective prevention and treatment. Under the supervision of an experienced mentoring team of expert scientists at the Baylor College of Medicine (BCM) and the University of Texas Medical Branch, the PI will be trained in the novel areas of metagenomics and microbiome, including didactic, laboratory techniques and analyses, with the future goal to independently lead a research program in microbiome of the respiratory tract, in relation to viral URI and AOM. Data will be generated on acquisition of nasopharyngeal microbiota in 150 infants in a Galveston birth cohort; half of whom developed AOM in the first year of life. Specific Aims are to characterize nasopharyngeal microbiota in infants followed from near birth up to 12 months of age and elucidate how changing patterns of nasopharyngeal bacterial colonization in infants lead to susceptibility to viral URI and AOM development. The outstanding metagenomics and microbiome facilities and expertise at the BCM, availability of sequential respiratory specimens from near birth, and the unique and complement environment at the two neighboring institutions will assure the project's success. Better understanding of the respiratory tract microbiota of young infants will facilitate the rationale design of new interventions to reduce colonization of pathogens, such as upper respiratory tract probiotics, or respiratory microbiota transplant, which, in turn, will help minimize the public health burden of AOM and other common childhood respiratory diseases.